Background

Australian funnel-web spiders (family Hexathelidae, subfamily Atracinae, genera Atrax and Hadronyche) are among the most venomous spiders in the world based on clinical experience in Australia,
[1] although their importance to human health is limited by their confined geographic range.
[2] Funnel-web spiders belong to the suborder Mygalomorphae, a primitive group of spiders that also includes tarantulas. Funnel-web spiders of medical importance comprise 40 species within 2 genera, Atrax and Hadronyche, in the family Hexathelidae, subfamily Atracinae. The Atrax genus contains 3 species, including Atrax robustus, the Sydney funnel-web spider. The remaining 37 species are members of the genus Hadronyche. Funnel-web spiders are primarily found on the eastern coast of Australia. Related funnel-web spiders can also be found in New Guinea and the Solomon Islands.

Funnel-web spiders are medium-to-large robust spiders that tend to be dark or black in color. These spiders measure up to 5 cm. They have stout legs and prominent fang-bearing chelicerae that deliver a neurotoxic venom. The common name derives from the funnel-like entrance to silk-lined subterranean burrows built by both males and females. The Sydney funnel-web spider (A robustus) is responsible for most reported envenomations and the only confirmed deaths in humans.
[3] The Sydney funnel-web spider is shown in the image below.

The Sydney funnel-web spider, Atrax robustus. Male (left) and female (right). Photograph courtesy of the Australian Venom Research Unit, Department of Pharmacology, University of Melbourne, Australia.

However, bites from other funnel-web spiders, particularly the northern tree spider, Hadronyche formidabilis, are likely to cause serious envenomation syndromes and are potentially deadly if untreated.

Bites from funnel-web spiders are rare. In Australia, a total of 138 funnel-web spider bites have been documented from 1926-2004.
[1] A prospective study revealed only 16 envenomations between 1999 and 2003
[4] ; 10-20% of bites produce toxicity. Male funnel-web spiders exhibit a seasonal wandering behavior in search of female mates, which often brings them into houses and in contact with humans. As a result, male spiders are responsible for most bites. Unfortunately, the venom of male spiders is apparently more toxic than that of female spiders. Humans and other primates suffer severe life-threatening toxicity from the venom, while other vertebrates, such as rabbits and cats, are almost unaffected. Only 13 fatalities have been attributed to the bite of a funnel-web spider.
[1] No fatalities have occurred since the introduction of an effective antivenin in 1981.
[1, 2]

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Pathophysiology

The venom component responsible for mortality and morbidity is a single peptide known as delta-hexatoxin (formerly delta-atracotoxin).
[5] Funnel-web spider antivenom, derived from purified immunoglobulin G (IgG) of rabbits hyperimmunized with A robustus venom , is also effective against venom of Hadronyche species. Delta-hexatoxins are polypeptide neurotoxins that induce spontaneous, repetitive firing and prolongation of action potentials in presynaptic autonomic and motor neurons.
[6, 7]

Delta-hexatoxin binds to the outer surface of tetrodotoxin-sensitive sodium channels. After binding, they induce excitability of these voltage-dependent sodium channels. The toxins also interfere with the conformational changes necessary for gating and inactivation of the channel. The ensuing massive neurotransmitter release results in an autonomic storm. The excessive release of endogenous acetylcholine, norepinephrine, and epinephrine is responsible for many of the clinical findings of funnel-web spider envenomation.

Envenomation is heralded by substantial pain at the bite site.
[1] Most funnel-web spider bites do not proceed to severe systemic symptoms, causing only mild or local neurotoxic effects. In severe cases, the onset of symptoms is rapid, with a median onset of 28 minutes.
[1] Agitation and vomiting are common. Autonomic effects include diaphoresis, salivation, piloerection, lacrimation, and pupillary changes. Cardiovascular changes commonly include hypertension and tachycardia. Hypotension and bradycardia occur more rarely. Pulmonary edema can occur in severe envenomations, with dyspnea and pink, frothy sputum often accompanied by respiratory failure. Skeletal muscle fasciculation, muscle spasms, and oral paresthesias are frequent neurologic findings. Coma or loss of consciousness occurs in about 10% of patients who experience severe envenomation.

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Epidemiology

Frequency

Funnel-web spiders of medical importance are found in eastern and southern Australia.
[8] The Sydney funnel-web spider (A robustus) is distributed in a roughly 75-mile radius around the city of Sydney. Hadronyche species have a much wider distribution, from southeast Queensland to Victoria, Tasmania, and parts of South Australia.

Sixteen confirmed cases of funnel-web spider bites were reported to poison control centers or hospitals in Australia from 1999-2003. A minority of patients (10-20%) require treatment with antivenom.
[4]

Age

Bites are equally common in adults and children. However, envenomation in children is more severe because of the greater venom load per kilogram of body mass. Children may experience life-threatening envenomation within an hour of the bite and require immediate treatment.

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Prognosis

Only 1 in 10 people bitten by a funnel-web spider displays signs of envenomation; however, if envenomation occurs, mortality rates are high in patients who receive no antivenom treatment. Most patients who survive until antivenom can be administered are able to make a complete recovery.

The mortality rate is difficult to determine from data from the era before antivenom. From 1927-1980, 13 deaths attributed to A robustus were reported in the medical literature and news media. No deaths have occurred since the introduction of antivenom.
[1]

Deaths occurred in children and adult females with bites. In all cases where the spider was identified, the culprit was the Sydney funnel-web spider, A robustus. Severe envenomation, but not death, has been reported following bites by Hadronyche species.

Death occurs between 15 minutes and 3 days following the bite. In children, death is usually early and caused by pulmonary edema. In adults, death usually occurs later and is caused by persistent hypotension and cardiovascular collapse. In the late 1970s, 2 deaths occurred despite modern intensive care units. Death in these cases occurred from multisystem organ failure days after the bite.
[9]